Abstract
We evaluated the efficacy of cefotaxime in the treatment of bacterial meningitis and the diffusion of the drug into CSF. Eleven children(9 days to 5 yrs) with meningitis due to H. influenzae (7 cases), S. pneumoniae(2) , group B streptococcus (1) , and Salmonella sp.(1), were treated with 40 mg/kg of IV cefotaxime q6hrs. Cefotaxime levels were determined by HPLC. The mean cefotaxime plasma level 3 hrs after a dose early in the treatment was 14.1 mg/L(range 5.1-42.2 mg/L), and the mean CSF level was 3.9 mg/L(0.7-16.6 mg/L). The mean CSF diffusion rate was 26.4%. At the end of treatment, the mean plasma level was 7.9 mg/L(1.5-13.6 mg/L) and the mean CSF level was 1.23 mg/L(0.5-3.1 mg/L) representing a mean diffusion rate of 21.9%. Cefotaxime MBC for the infecting organisms ranged between 0.015 mg/L and 0.25 mg/L. CSF was bactericidal to the infecting organisms at dilutions between 8 and 256. The CSF diffusion correlated positively with the cefotaxime plasma level (r=0.86), CSF protein (r=0.63), CSF leukocyte count (r=0.61) and negatively with CSF sugar (r=-0.37).All patients responded well to treatment with no apparent sequelae.
Serial levels were also determined in 5 infants with ventriculostomies. Following a single dose of 40 mg/kg, the mean cefotaxime CSF levels (and mean plasma levels) were 6.6 mg/L(28.4 mg/L) at 2 hrs, 5.7 mg/L(8.9 mg/L) at 4 hrs, and 4.5 mg/L (1.8 mg/L) at 6 hrs. Cefotaxime diffuses sufficiently and consistently into CSF. Further assessment of its efficacy in the treatment of childhood meningitis is warranted.